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Leonardo A Martínez, Elena Larrieta, David Kershenobich, Aldo Torre
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses: fatty liver (SS), steatohepatitis (NASH) with or without fibrosis and cirrhosis. Patatine-like phosphatas in domain 3 (PNPLA3; adiponutrin; SNP rs738409 C/G, M148I) shows anabolic and catabolic activities on lipid metabolism and significant association to fatty liver content; however, I148M demographics and ethnics, as its role with NAFLD have not been fully elucidated. MATERIAL AND METHODS: PNPLA3 genotyping from peripheral blood DNA by polymerase chain reaction (PCR) and direct sequencing, 211 patients diagnosed with NAFLD including SS, NASH and fibrosis spectrum...
November 2017: Annals of Hepatology
Agnieszka Budny, Piotr Kozłowski, Marzena Kamińska, Małgorzata Jankiewicz, Agnieszka Kolak, Bożena Budny, Witold Budny, Joanna Niemunis-Sawicka, Grzegorz Szczypiór, Bartosz Kurniawka, Franciszek Burdan
Primary liver neoplasms occurs relatively rarely in Poland. The most frequently occurring type of cancer is hepatocellular carcinoma (HCC), which globally constitutes 7% of all the occurrences of cancer. The incidence increases with age and is the highest in patients around the age of 70. It also varies significantly depending on the geographic location. The main factors that cause HCC are infection of HBV and HCV, whose genome integrates into the DNA of the host, causing mutations. The other factors include excessive alcohol consumption, contact or consumption of Aspergillus toxins as well as various metabolic disorders, such as α1-antitrypsin deficiency, hemochromatosis, tyrosinemia, porphyria, von Gierke disease and in person with gene mutation p...
September 29, 2017: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Hironori Mitsuyoshi, Kohichiroh Yasui, Tasuku Hara, Hiroyoshi Taketani, Hiroshi Ishiba, Akira Okajima, Yuya Seko, Atsushi Umemura, Taichiro Nishikawa, Kanji Yamaguchi, Michihisa Moriguchi, Masahito Minami, Yoshito Itoh
AIM: To examine the role of nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: Levels of mRNAs encoding NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain, procaspase-1, interleukin (IL)-1β, and IL-18 were quantified by real-time polymerase chain reaction in 91 liver samples and 37 blood samples from biopsy-proven patients with NAFLD...
December 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Enrique Jurado-Ruiz, Lourdes M Varela, Amparo Luque, Genoveva Berná, Gladys Cahuana, Enrique Martinez-Force, Rocío Gallego-Durán, Bernat Soria, Baukje de Roos, Manuel Romero Gómez, Franz Martín
SCOPE: We evaluated the protective effect of extra virgin olive oil (EVOO) in high-fat diets (HFDs) on the inflammatory response and liver damage in a nonalcoholic fatty liver disease (NAFLD) mouse model. METHODS AND RESULTS: C57BL/6J mice were fed a standard diet or a lard-based HFD (HFD-L) for 12 wk to develop NAFLD. HFD-fed mice were then divided into four groups and fed for 24 wk with the following: HFD-L, HFD-EVOO, HFD based on phenolics-rich EVOO, and reversion (standard diet)...
March 2017: Molecular Nutrition & Food Research
Huaibo Yuan, Wenjuan Wang, Deyi Chen, Xiping Zhu, Lina Meng
BACKGROUND: Enteric dysbiosis is associated with chronic inflammation and interacts with obesity and insulin resistance. Obesity and diabetes are induced in ICR (Institute of Cancer Research) mice fed a high-fat diet and administered a streptozocin injection. These mice were treated with normal rice (NR), normal rice with a high resistant starch content (NRRS) or Se-rich rice (selenium-enriched rice) with a high resistant starch content (SRRS). RESULTS: Faecal cell counts of Bifidobacterium, Lactobacillus and Enterococcus were significantly higher in SRRS-treated mice than in diabetic controls, while Enterobacter cloacae were lower...
May 2017: Journal of the Science of Food and Agriculture
Arianna Mazzotti, Maria Turchese Caletti, Anna Simona Sasdelli, Lucia Brodosi, Giulio Marchesini
BACKGROUND: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors). KEY MESSAGES: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets...
2016: Digestive Diseases
Verena Wieser, Timon E Adolph, Barbara Enrich, Patrizia Moser, Alexander R Moschen, Herbert Tilg
BACKGROUND & AIMS: Obesity and its related co-morbidities such as non-alcoholic fatty liver disease (NAFLD) are increasing dramatically worldwide. The genetic variation in Patatin-like phospholipase domain-containing protein 3 (PNPLA3), which is also called adiponutrin (ADPN), in residue 148 (I148M, rs738409) has been associated with NAFLD. However, the regulation and function of PNPLA3 in metabolic diseases remains unclear. Laparoscopic gastric banding (LAGB) of severely obese patients reduces body weight, liver and adipose tissue inflammation...
February 2017: Liver International: Official Journal of the International Association for the Study of the Liver
Marcin Krawczyk, Ewa Stachowska, Piotr Milkiewicz, Frank Lammert, Malgorzata Milkiewicz
BACKGROUND: The adiponutrin (PNPLA3) p.I148M and transmembrane 6 superfamily member 2 (TM6SF2) p.E167K variants represent risk factors for non-alcoholic fatty liver disease (NAFLD). In this study, we assessed the effects of caloric restriction on liver phenotypes in NAFLD patients in relation to the PNPLA3 and TM6SF2 genotypes. METHODS: We genotyped both variants in 143 individuals with NAFLD (55 females, age 18-74 years) and 180 controls (85 females, age 33-66 years)...
2016: Digestion
Hong-Guang Li, Fang-Feng Liu, Hua-Qiang Zhu, Xu Zhou, Jun Lu, Hong Chang, Jin-Hua Hu
ADPN I148M polymorphism has been consistently reported to play a role in liver-associated diseases, such as alcoholic liver disease, chronic hepatitis C, and liver fat and fibrosis in nonalcoholic fatty liver disease. This significant association was also indicated in a series of hepatocellular carcinoma (HCC) studies, where the significance may be affected due to the small sample sizes. The aim of this study was to reexamine the ADPN-HCC association by use of meta-analysis. Biweekly computer-based literature searches plus manual screening were undertaken in an effort to identify all studies that met the predefined inclusion criteria...
November 2015: Medicine (Baltimore)
Atanu Kumar Dutta
Alcoholic liver disease is a major source of morbidity and mortality worldwide. Twin studies had demonstrated heritability of alcoholic liver disease. Although to date only Adiponutrin (PNPLA3) rs738409 polymorphism (I148M) had been unequivocally proved to be associated with increased risk of alcoholic liver disease across different ethnicities. This protein was previously thought to have a predominant lipolytic role. However, recent investigations have provided evidence of lipogenic activity of this protein...
December 2015: Medical Hypotheses
Elena L Enache, Anca Sin, Ligia Bancu, Christophe Ramière, Olivier Diaz, Patrice André, Liviu S Enache
Chronic hepatitis C (CHC) is a major burden for public health worldwide. Although newer direct-acting antivirals show good efficacy, their cost precludes their wide adoption in resource-limited regions. Thus, strategies are being developed to help identify patients with high susceptibility to response to classic PEG-interferon + ribavirin therapy. IL28B polymorphism rs12979860 C/T is an important predictor for an efficient response to interferon-based therapy. A genetic variant in adiponutrin (PNPLA3) gene, rs738409 C/G, is associated with steatosis, severity, and progression of liver fibrosis in CHC patients, and predicts treatment outcome in difficult-to-cure HCV-infected patients with advanced fibrosis...
2015: International Journal of Molecular Sciences
Tsunehiro Ochi, Kensuke Munekage, Masafumi Ono, Takuma Higuchi, Masayuki Tsuda, Yoshihiro Hayashi, Nobuto Okamoto, Katsumi Toda, Shuji Sakamoto, Jude A Oben, Toshiji Saibara
AIM: Non-alcoholic steatohepatitis (NASH) is the major cause of chronic liver disease worldwide. Endoplasmic reticulum (ER) stress is considered to be an important pathological characteristic in NASH. A sequence variation (I148M) in the patatin-like phospholipase domain-containing protein 3/adiponutrin (PNPLA3) gene is known to be associated with the development of NASH. However, PNPLA3 deficiency has been considered to not be associated with fatty liver disease. To clarify, therefore, the role of PNPLA3 in liver, we established PNPLA3 knockout (KO) mice and investigated the phenotypes and involved factors under ER stress...
May 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
Marcin Krawczyk, Roman Liebe, Ina B Maier, Anna Janina Engstler, Frank Lammert, Ina Bergheim
Introduction. The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. Here, we investigate the association of this polymorphism with hepatic and metabolic traits in a pediatric cohort. Patients and Methods. The study cohort comprised 142 German children (age 5-9 years, 98 overweight, 19 children with NAFLD). Results. Overweight children presented with increased serum ALT (P = 0.001) and GGT (P < 0.001) activities. ALT activities differed significantly (P = 0.02) between carriers of different PNPLA3 genotypes in the entire study cohort, in normal weight children (P = 0...
2015: Gastroenterology Research and Practice
Anita Arslanow, Caroline S Stokes, Susanne N Weber, Frank Grünhage, Frank Lammert, Marcin Krawczyk
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is becoming the most prevalent liver disorder. The PNPLA3 (adiponutrin) variant p.I148M has been identified as common genetic modifier of NAFLD. Our aim was to assess the relationships between genetic risk and non-invasively measured liver fat content. METHODS: Hepatic steatosis was quantified by transient elastography, using the controlled attenuation parameter (CAP) in 174 patients with chronic liver diseases (50% women, age 18-77 years)...
March 2016: Liver International: Official Journal of the International Association for the Study of the Liver
Stefan Traussnigg, Christian Kienbacher, Emina Halilbasic, Christian Rechling, Lili Kazemi-Shirazi, Harald Hofer, Petra Munda, Michael Trauner
Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and comprises a liver disease spectrum ranging from steatosis to nonalcoholic steatohepatitis (NASH) with risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Associated metabolic conditions and comorbidities such as obesity, diabetes and cardiovascular diseases are common and require concerted management. Adiponutrin (PNPLA3) variants may help to identify NAFLD patients at higher risk for liver disease progression towards advanced fibrosis and HCC...
2015: Digestive Diseases
Felix Stickel, Jochen Hampe, Eric Trépo, Christian Datz, Stefano Romeo
Alcoholic liver disease (ALD) accounts for the majority of chronic liver diseases in Western countries, and alcoholic cirrhosis is among the premier causes of liver failure, hepatocellular carcinoma (HCC) and liver-related mortality causes. Studies in different genders and ethnic groups, as well as in twins provide strong evidence for a significant contribution of host genetic factors to liver disease development in drinkers. The intense quest for genetic modifiers of alcohol-induced fibrosis progression have identified and repeatedly confirmed a genetic polymorphism in the gene coding for patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin; rs738409 C/G, M148I) as a risk factor for alcoholic cirrhosis and its related complication, HCC, in different populations...
June 2015: Hepatobiliary Surgery and Nutrition
Ching-Jung Hsieh, Pei Wen Wang, Tsung Hui Hu
OBJECTIVE: Patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) have a higher prevalence of cardiovascular diseases. In this study we investigated the frequency of single nucleotide polymorphisms (SNPs) of several candidate genes associated with NAFLD in Taiwanese patients with type 2 diabetes mellitus (DM) and NAFLD and in those with DM but without fatty liver disease. METHODS: We enrolled 350 patients with type 2 DM and NAFLD and 209 patients with DM but without NAFLD...
2015: PloS One
Ning Geng, Yong-Ning Xin, Harry Hua-Xiang Xia, Man Jiang, Jian Wang, Yang Liu, Li-Zhen Chen, Shi-Ying Xuan
CONTEXT: The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established. EVIDENCE ACQUISITION: We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine...
April 2015: Hepatitis Monthly
S Petta, E Vanni, E Bugianesi, C Rosso, D Cabibi, C Cammà, V Di Marco, M Eslam, S Grimaudo, F S Macaluso, D McLeod, R M Pipitone, M L Abate, A Smedile, J George, A Craxì
BACKGROUND: The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). AIM: To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis...
May 2015: Alimentary Pharmacology & Therapeutics
Simona Bo, Roberto Gambino, Guido Menato, Stefania Canil, Valentina Ponzo, Silvia Pinach, Marilena Durazzo, Ezio Ghigo, Maurizio Cassader, Giovanni Musso
BACKGROUND: A single nucleotide polymorphism (SNP) of the patatin-like phospholipase-3 (PNPLA3)/adiponutrin gene (rs738409 C>G) is strongly associated with nonalcoholic fatty liver disease; to our knowledge, no data are available on the impact of this PNPLA3 SNP on liver and metabolic outcomes during pregnancy in patients with gestational diabetes (GD). OBJECTIVE: We evaluated the impact of the PNPLA3 rs738409 SNP on liver enzymes, metabolic indexes, and maternal and neonatal outcomes in 200 GD patients enrolled in a lifestyle intervention...
February 2015: American Journal of Clinical Nutrition
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